Ganglioside GD3 and its mimetics induce cytochrome c release from mitochondria

Yutaka Inoki, Tsuyoshi Miura, Tetsuya Kajimoto, Mitsuo Kawase, Yuji Kawase, Yasuko Yoshida, Shuichi Tsuji, Tadatoshi Kinouchi, Hitoshi Endo, Yasuo Kagawa, Toshiro Hamamoto

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15 Citations (Scopus)


Ganglioside GD3 induced the release of cytochrome c from isolated rat liver mitochondria. This process was completely prevented by cyclosporin A and partially prevented by a cysteine protease inhibitor, n-acetyl-leu-leu-norleucinal. Cyclosporin A is a potent inhibitor of the permeability transition pore, whereas n-acetyl-leu-leu-norleucinal has no effect on this pore. These results indicate that the release of cytochrome c from mitochondria requires both the opening of the permeability transition pore and a cysteine protease inhibitor-sensitive mechanism. Gangliosides GD1a, GD1b, GT1b, and GQ1b along with the synthetic GD3 mimetics TMS-42 and CI-22, which are glycerophospholipids carrying a disialo residue, also induced cytochrome c release. In contrast, gangliosides GM1, GM2, and GM3 did not induce cytochrome c release. These results indicate that two sialo residues must play an important role in the induction of cytochrome c release by gangliosides. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)1210-1216
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2000 Oct 5


  • Apoptosis
  • Cystein protease
  • Cytochrome c
  • Gangliosides
  • Mitochondrial permeability transition


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